SHP-1 (PTP1C, SH-PTP1, SHP, HCP) and SHP-2 (PTP2C, SH-PTP-2, PTP1D, Syp, SH-PTP-3) are two SH2 domain containing protein tyrosine phosphatases (PTPs) which have crucial roles in signal transduction. The goal of this study is to investigate the role of these enzymes in the signaling of platelet derived growth factor (PDGF). The experimental approach is to co-express transiently the PDGF receptor with native, truncated, mutated, chimeric, and hybrid forms of the enzymes in a well established 293 cell expression system. Such gene manipulations are intended to change the activity, substrate specificity, regulation, ability to interact with other proteins, and localization of SHP-1 and SHP-2. The objectives are to determine the effects of such altered PTP expressions on tyrosine phosphorylation of the PDGF receptor and on activation of the Ras/MAP kinase and JAK-STAT signaling pathways. By correlating activity of the PTPs, tyrosine phosphorylation of the PDGF receptor and activation of MAP kinase STATs, the intent is to obtain a better understanding of the regulatory mechanism of SHP-1 and SHP-2, better define the distinct functions of the enzymes, delineate the roles of individual phosphorylation sites of PDGF-R and proteins recruited to the sites, and produce more complete diagrams for the two major signal transduction pathways.